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AMX0035 and oral edaravone for amyotrophic lateral sclerosis: final evidence report
AMX0035 and oral edaravone for amyotrophic lateral sclerosis: final evidence report
- Collection:
- Health Policy and Services Research
- Author(s):
- Makam, Anil N., author
Nikitin, Dmitriy, author
Richardson, Marina, author
Mohammed, Rasheed, author
McKenna, Avery, author
Pearson, Steven D., author
Rind, David M., author
Suh, Kangho, author
Carlson, Josh J., author - Contributor(s):
- Institute for Clinical and Economic Review, issuing body.
Midwest Comparative Effectiveness Public Advisory Council, issuing body. - Publication:
- [Boston, Massachusetts] : Institute for Clinical and Economic Review, September 13, 2022
- Language(s):
- English
- Format:
- Text
- Subject(s):
- Amyotrophic Lateral Sclerosis -- drug therapy
Drug Therapy, Combination
Edaravone -- therapeutic use
Phenylbutyrates -- therapeutic use
United States - Genre(s):
- Technical Report
- Abstract:
- Amyotrophic lateral sclerosis (ALS) is a rare, rapidly progressive, and fatal neurodegenerative disease characterized by loss of motor neurons in the brain and spinal cord. ALS most commonly presents with localized weakness that progresses to muscle paralysis, respiratory failure, and death. In addition to weakness, up to 15% develop frontotemporal dementia. The etiology of most ALS is unknown. In the United States, there are approximately 25,000 people living with ALS. Age is the strongest risk factor for developing ALS, with the highest prevalence between 60 and 79 years of age. The average life expectancy is three to five years after symptom onset. As the disease progresses, there is a considerable need for caregiving, both paid and unpaid, with significant caregiver burden. Current treatment of ALS is largely focused on supportive care, which includes symptom management, nutritional support, and noninvasive ventilation to treat respiratory failure, ideally provided in a multidisciplinary ALS clinic. Riluzole and edaravone (Radicava®) are the only two Food and Drug Administration (FDA)-approved therapies that modestly slow disease progression, and riluzole is the only drug thought to prolong survival (average of two to three months). Most patients take riluzole, but edaravone has been used much less because of the burden of intravenous infusion. The FDA recently approved an oral formulation based on bioequivalence with the IV formulation. AMX0035, an oral combination of sodium phenylbutyrate (PB) and taurursodiol (TURSO) taken up to twice daily, is under FDA review with an expected decision date by September 29, 2022. AMX0035 was evaluated in the CENTAUR trial, a 24-week randomized controlled trial (RCT), and in the companion open-label extension, CENTAUR-OLE. The primary outcome was progression of ALS, and treatment moderately reduced progression, although the statistical significance of this reduction varied depending on the analysis. As a secondary outcome, CENTAUR-OLE assessed death based on the original randomization in CENTAUR, a conservative analysis, and found a 4.8- month survival benefit (hazard ratio 0.64, p=0.048). AMX0035 appears to have minimal harms. The evidence base for the efficacy of oral edaravone was derived from three RCTs of intravenous edaravone: Studies 16 (early-stage ALS), 18 (late-stage ALS), and 19. Studies 16 and 18 showed no benefit of edaravone on progression of ALS, however a post-hoc analysis of Study 16 raised the possibility of benefit in a narrow subgroup of early-onset ALS patients. Treatment of this subgroup was evaluated in Study 19, and edaravone moderately reduced progression. There were too few deaths to assess survival, however an observational study of edaravone found no evidence of a reduction in mortality. Oral edaravone appears to have minimal harms.
- Copyright:
- Reproduced with permission of the copyright holder. Further use of the material is subject to CC BY license. (More information)
- Extent:
- 1 online resource (1 PDF file (various pagings))
- Illustrations:
- Illustrations
- NLM Unique ID:
- 9918506283306676 (See catalog record)
- Permanent Link:
- http://resource.nlm.nih.gov/9918506283306676